Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Article Reviewed:

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Effects of the prone position on gas exchange and hemodynamics in severe acute respiratory distress syndrome.

Jolliet P, Bulpa P, Chevrolet JC.

Crit Care Med 1998;26:1977-85. [abstract]

Reviewed by Varsha Gharpure, MD and Kathleen Meert, MD, Children's Hospital of Michigan

Review posted October 2, 1999

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I. What is being studied?:

The study objective:

To address the following issues regarding the use of prone position ventilation in-patients with severe acute respiratory distress syndrome (ARDS):

1. Response rate
2. Magnitude and duration of improved oxygenation in responders during a 12 hour trial and the consequences of returning to the supine position
3. Association of the prone position with modification of gas exchange and hemodynamics
4. Signs of substantial worsening of gas exchange and/or hemodynamics in nonresponder
5. Response to the initial trial predictive of the response to subsequent trials

The study design:

Prospective, nonrandomized interventional study.

The patients included:

Nineteen consecutive, mechanically ventilated patients (age 45 +/- 20 years) with ARDS and severe hypoxemia defined as:

1. PaO2/FiO2 of 150,
2. with FiO2 of 0.6,
3. persisting for 24 hrs,

and a pulmonary artery occlusion pressure of <18 mm Hg.

The patients excluded:

1. Asthma
2. Severe chronic obstructive pulmonary disease(forced expiratory volume in 1 sec was < 1 L)
3. Pulmonary abscess
4. Hemoptysis
5. Alveolar hemorrhage
6. Extensive skin lesions

The interventions compared:

Patients were turned prone. After 2 hours non-responders were returned to supine position. Responders were maintained in prone position for 12 hours before being returned to the supine position.

The procedure was repeated on a daily basis in all patients, until inclusion criteria were no longer met or the patients died.

The outcomes evaluated:

Primary outcome measures:

1. Response to prone positioning, defined as:
   • PaO2 increase 10 torr, or
   • Increase in PaO2/FiO2 ratio of 20
2. Magnitude and duration of improved oxygenation in responders

Secondary outcome measures:

1. Changes in hemodynamic measurements
   • Heart rate
   • Cardiac index
   • Systemic and pulmonary vascular resistance
   • Central venous pressure
   • Mean arterial pressure
   • Mean pulmonary arterial pressure
   • Venous admixture
2. Response to initial trial predictive of the response to subsequent trials

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

No. The intervention was not randomized across patients or within the same patient.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

No. Follow up was less than complete. Authors have given the final outcome in all patients - dead or survived. However cause of death in every patient (respiratory or non-respiratory) is not provided. Even though they were looking at only short term physiology and not a long-term outcome, it is still important to know if responders died from respiratory or a non-respiratory multisystem involvement.

Were patients analyzed in the groups to which they were randomized?

There was no randomization of subjects in this study.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

No. Study personnel were involved in the care of the patient and were aware if the patient was supine or prone when the data was collected.

4. Were the groups similar at the start of the trial?

There is no control group in this study.

5. Aside from the experimental intervention, were the groups treated equally?

Again there is no control group. Patients were compared regarding their oxygenation and hemodynamic status when supine and after turning prone. The only systematic clinical intervention in this before and after design is turning the patient prone.

III. What were the results?

1. How large was the treatment effect?

Primary outcome measures:

1. Response to initial therapy: Out of 19 patients who were turned prone for the first time, 11(57%) responded and 9 did not.
2. Magnitude and duration of improved oxygenation in responders:
   • Mean PaO2 change has been given separately in responders and non-responders. Hence information on mean change in PaO2 before and after change of position in all treated patients is not available.
   • In 11 responders, mean PaO2 increased from 58+6 to 78+11 within first 30 minutes and to 81+8 at the end of 2 hours. On return to supine position PaO2 was 70+7. In 8 non-responders PaO2 did not change. The maximal improvement in oxygenation was seen at 30 minutes and maintained for the whole 12 hours.

It is not possible to calculate relative risk reduction, absolute risk reduction, and number needed to treat since there was no control group and this was a physiologic effect study only.

In the inclusion criteria authors have mentioned that PaO2/FiO2 remained < 150 for 24 hours prior to enrollment. So a patient with PaO2/FiO2 ratio of 60 which improved to 80 in 24 hours prior to study could still meet the criteria for inclusion. If he then improved from 80 to 90 after turning, he would be considered a responder. However his PaO2 may have been on an upward trend and the further increase was unrelated to turning. From the inclusion criteria of the study it is not clear whether PaO2/FiO2 ratio in these patients was improving, steady or deteriorating.

Secondary outcome measures:

1. Hemodynamic measurements:
   • Venous admixture reduced from 50 +/- 10 to 40 +/- 9 at the end of 30 minutes in 11 responders.
   • There was no change in other hemodynamic parameters during the entire protocol either in responders or non-responders. There was no increase in vasoactive drug administration.
2. Response to initial trial predictive of the response to subsequent trials
   • Total of 28 additional episodes of prone positioning were performed in 19 patients. Twenty-four of these episodes were performed in the responders with a response to 17/24 episodes (71%). Four episodes were performed in the non-responders with a response to only 1(25%). Authors have concluded that a response to initial trial was not predictive of response to subsequent trials. Absence of initial response was however mostly predictive of absence of subsequent response. However only 4 episodes of repeat trial were performed in 2 initial non-responders. Also 24 repeat episodes among responders were performed in only 6 patients. Eleven of these are accounted by only one patient. Thus sample size is too small to draw any such conclusion.
3. Mortality rate overall was 79%; 73% of responders and 87% of non-responders. There were no discernable differences between responders and non-responders in age, APACHE II scores, or any other measured physiologic variable.

2. How precise was the estimate of the treatment effect?

Typical confidence intervals cannot be calculated, as there was no binary treatment effects assessed.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

No. This study involves adult patients and it is hard to extend the same conclusion to pediatric patients. Even in adult population the benefits are not clearly evident. The authors have used improved oxygenation as the outcome measure. The ultimate clinical end points are: reduction in the mortality and residual lung damage in the survivors. ARDS is very often part of multisystem organ failure syndrome. Thus improved oxygenation may not have a strong independent, consistent association with reduction in mortality. Also there are many unanswered questions like how often they should be turned? How long they should be turned? Whether children will have a similar response? Will it reduce invasive interventions like ECMO? Will it reduce number of days on the mechanical ventilator?

Improvement in oxygenation on prone positioning is however an important physiological observation warranting a randomized controlled trial addressing many more unanswered question.

2. Were all clinically important outcomes considered?

No. This is only a study assessing the effect of an intervention on a physiological parameter - oxygenation.

3. Are the likely treatment benefits worth the potential harms and costs?

No. Treatment benefits were not clearly evident in this study. Authors did not find any adverse effects except transient hemodynamic instability in 2 patients, which rapidly corrected. Complications of prone positioning have however been demonstrated by other studies. These include obstruction, kink or accidental extubation of the endotracheal tube, pneumothorax secondary to obstructed chest tube, apical atelectasis, accidental femoral artery catheter removal, and catheter compression preventing infusion of the catecholamines (1,2). Stocker et al reported 2 serious complications. One patient developed infectious corneal ulceration needing immediate corneal transplant and one patient with abdominal infection went in septic shock after being turned prone (3). Thus process of turning prone may not be as easy and innocuous, as it seems to be.

References

1. Jolliet P, Bulpa P, Ritz M, et al: Additive beneficial effects of the prone position, nitric oxide, and almitrine bismesylate on gas exchange and oxygen transport in acute respiratory distress syndrome. Crit Care Med 1997; 25: 786-794. [abstract]
2. Chatte G, Sab J-M, Dubois J-M, et al: Prone position in mechanically ventilated patients with severe acute respiratory failure. Am Rev Respir Dis 1997; 155:473-478. [abstract]
3. Stocker R, Neff T, Stein S, et al: Prone positioning and low-volume pressure-limited ventilation improve survival in-patients with severe ARDS. Chest 1997; 111:1008-1017. [abstract]

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